Differential effects of chaperones on yeast prions: CURrent view

  • Andrew G. Matveenko
  • Yury A. Barbitoff
  • Lina Manuela Jay-Garcia
  • Yury O. Chernoff
  • Galina A. Zhouravleva
Review

Abstract

Endogenous yeast amyloids that control heritable traits and are frequently used as models for human amyloid diseases are termed yeast prions. Yeast prions, including the best studied ones ([PSI +] and [URE3]), propagate via intimate interactions with molecular chaperones. Different yeast prions exhibit differential responses to changes in levels, functionality or localization of the components of chaperone machinery. Here, we provide additional data confirming differential effects of chaperones (and specifically, Hsp40s) on yeast prions and summarize current knowledge of the mechanisms underlying chaperone specificities. Contrary to frequent statements in literature, overproduction of the Hsp104 chaperone antagonizes both [PSI +] and [URE3] prions, while overproduction of the Hsp70-Ssa1 chaperone antagonizes [URE3] prion only in some, but not in all strains. Recently, we demonstrated that the relocalization of a fraction of the Hsp40 chaperone Sis1 from the cytosol to the nucleus by the chaperone-sorting factor Cur1 exhibits opposite effects on [PSI +] and [URE3] prions. We suggest that the response of prions to changes in Sis1 localization represents a combination of the effects of Sis1 shortage on fragmentation of prion aggregates and on malpartition of prion aggregates during a cell division. Differences in sensitivity of prion fragmentation to Sis1 and in relative inputs of fragmentation and malpartition in prion propagation result in opposite effects of Sis1 relocalization on [PSI +] and [URE3].

Keywords

Yeast prion Molecular chaperone Hsp40 Hsp70 Cur1 

Notes

Acknowledgements

We thank Rebecca L. Howie and Gary P. Newnam for help in some experiments, Simon Alberti for the YAL-456 strain, and Varvara E. Tvorogova for the pGADT7-GW plasmid. This work was supported by St. Petersburg State University (projects 15.61.2218.2013, 1.37.291.2015, and 1.40.1327.2017) and grants from the Russian Foundation for Basic Research (16-04-00202, 15-04-00650 and 15-04-08159), Russian Science Foundation (14-50-00069), and National Science Foundation (MCB 1516872). Technical help was provided by Resource Centers “Development of Molecular and Cell Technologies” and “Biobank” of St. Petersburg State University.

References

  1. Amor AJ, Castanzo DT, Delany SP, Selechnik DM, van Ooy A, Cameron DM (2015) The ribosome-associated complex antagonizes prion formation in yeast. Prion 9:144–164. doi: 10.1080/19336896.2015.1022022 CrossRefPubMedPubMedCentralGoogle Scholar
  2. Barbitoff YA, Matveenko AG, Moskalenko SE, Zemlyanko OM, Newnam GP, Patel A, Chernova TA, Chernoff YO, Zhouravleva GA (2017) To CURe or not to CURe? Differential effects of the chaperone sorting factor Cur1 on yeast prions are mediated by the chaperone Sis1. Mol Microbiol 105:242–257. doi: 10.1111/mmi.13697 CrossRefPubMedGoogle Scholar
  3. Brachmann A, Baxa U, Wickner RB (2005) Prion generation in vitro: amyloid of Ure2p is infectious. EMBO J 24:3082–3092. doi: 10.1038/sj.emboj.7600772 CrossRefPubMedPubMedCentralGoogle Scholar
  4. Cheetham ME, Caplan AJ (1998) Structure, function and evolution of DnaJ: conservation and adaptation of chaperone function. Cell Stress Chaperones 3:28–36CrossRefPubMedPubMedCentralGoogle Scholar
  5. Chernoff YO, Kiktev DA (2016) Dual role of ribosome-associated chaperones in prion formation and propagation. Curr Genet 62:677–685. doi: 10.1007/s00294-016-0586-2 CrossRefPubMedGoogle Scholar
  6. Chernoff YO, Lindquist SL, Ono BI, Inge-Vechtomov SG, Liebman SW (1995) Role of the chaperone protein Hsp104 in propagation of the yeast prion-like factor [PSI +]. Science 268:880–884CrossRefPubMedGoogle Scholar
  7. Chernova TA, Wilkinson KD, Chernoff YO (2017) Prions, chaperones, and proteostasis in yeast. Cold Spring Harb Perspect Biol 9:a023663. doi: 10.1101/cshperspect.a023663 CrossRefPubMedGoogle Scholar
  8. Cox B, Tuite M (2017) The life of [PSI]. Curr Genet. doi: 10.1007/s00294-017-0714-7 PubMedGoogle Scholar
  9. Craig EA, Marszalek J (2017) How do J-proteins get Hsp70 to do so many different things? Trends in Biochem Sci 42:355–368. doi: 10.1016/j.tibs.2017.02.007 CrossRefGoogle Scholar
  10. Duennwald ML, Echeverria A, Shorter J (2012) Small heat shock proteins potentiate amyloid dissolution by protein disaggregases from yeast and humans. PLoS Biol 10:e1001346. doi: 10.1371/journal.pbio.1001346 CrossRefPubMedPubMedCentralGoogle Scholar
  11. Gorkovskiy A, Reidy M, Masison DC, Wickner RB (2017) Hsp104 disaggregase at normal levels cures many [PSI+] prion variants in a process promoted by Sti1p, Hsp90, and Sis1p. Proc Natl Acad Sci USA 114:E4193–E4202. doi: 10.1073/pnas.1704016114 CrossRefPubMedGoogle Scholar
  12. Harris JM, Nguyen PP, Patel MJ, Sporn ZA, Hines JK (2014) Functional diversification of Hsp40: distinct J-protein functional requirements for two prions allow for chaperone-dependent prion selection. PLoS Genet 10:e1004510. doi: 10.1371/journal.pgen.1004510 CrossRefPubMedPubMedCentralGoogle Scholar
  13. Higurashi T, Hines JK, Sahi C, Aron R, Craig EA (2008) Specificity of the J-protein Sis1 in the propagation of 3 yeast prions. Proc Natl Acad Sci USA 105:16596–16601. doi: 10.1073/pnas.0808934105 CrossRefPubMedPubMedCentralGoogle Scholar
  14. Hung G, Masison DC (2006) N-terminal domain of yeast Hsp104 chaperone is dispensable for thermotolerance and prion propagation but necessary for curing prions by Hsp104 overexpression. Genetics 173:611–620. doi: 10.1534/genetics.106.056820 CrossRefPubMedPubMedCentralGoogle Scholar
  15. James P, Halladay J, Craig EA (1996) Genomic libraries and a host strain designed for highly efficient two-hybrid selection in yeast. Genetics 144:1425–1436PubMedPubMedCentralGoogle Scholar
  16. Kabani M, Melki R (2016) More than just trash bins? Potential roles for extracellular vesicles in the vertical and horizontal transmission of yeast prions. Curr Genet 62:265–270. doi: 10.1007/s00294-015-0534-6 CrossRefPubMedGoogle Scholar
  17. Kiktev DA, Chernoff YO, Archipenko AV, Zhouravleva GA (2011) Identification of genes influencing synthetic lethality of genetic and epigenetic alterations in translation termination factors in yeast. Dokl Biochem Biophys 438:117–119. doi: 10.1134/S1607672911030021 CrossRefPubMedPubMedCentralGoogle Scholar
  18. Kiktev DA, Melomed MM, Lu CD, Newnam GP, Chernoff YO (2015) Feedback control of prion formation and propagation by the ribosome-associated chaperone complex. Mol Microbiol 96:621–632. doi: 10.1111/mmi.12960 CrossRefPubMedPubMedCentralGoogle Scholar
  19. Kirkland PA, Reidy M, Masison DC (2011) Functions of yeast Hsp40 chaperone Sis1p dispensable for prion propagation but important for prion curing and protection from prion toxicity. Genetics 188:565–577. doi: 10.1534/genetics.111.129460 CrossRefPubMedPubMedCentralGoogle Scholar
  20. Kryndushkin DS, Shewmaker F, Wickner RB (2008) Curing of the [URE3] prion by Btn2p, a Batten disease-related protein. EMBO J 27:2725–2735. doi: 10.1038/emboj.2008.198 CrossRefPubMedPubMedCentralGoogle Scholar
  21. Kryndushkin DS, Engel A, Edskes H, Wickner RB (2011) Molecular chaperone Hsp104 can promote yeast prion generation. Genetics 188:339–348. doi: 10.1534/genetics.111.127779 CrossRefPubMedPubMedCentralGoogle Scholar
  22. Liebman SW, Chernoff YO (2012) Prions in yeast. Genetics 191:1041–1072CrossRefPubMedPubMedCentralGoogle Scholar
  23. Malinovska L, Kroschwald S, Munder MC, Richter D, Alberti S (2012) Molecular chaperones and stress-inducible protein-sorting factors coordinate the spatiotemporal distribution of protein aggregates. Mol Biol Cell 23:3041–3056. doi: 10.1091/mbc.E12-03-0194 CrossRefPubMedPubMedCentralGoogle Scholar
  24. Masison DC, Reidy M (2015) Yeast prions are useful for studying protein chaperones and protein quality control. Prion 9:174–183. doi: 10.1080/19336896.2015.1027856 CrossRefPubMedPubMedCentralGoogle Scholar
  25. Miller SB, Ho CT, Winkler J, Khokhrina M, Neuner A, Mohamed MY, Guilbride DL, Richter K, Lisby M, Schiebel E, Mogk A, Bukau B (2015) Compartment-specific aggregases direct distinct nuclear and cytoplasmic aggregate deposition. EMBO J 34:778–797. doi: 10.15252/embj.201489524 CrossRefPubMedPubMedCentralGoogle Scholar
  26. Moosavi B, Wongwigkarn J, Tuite MF (2010) Hsp70/Hsp90 co-chaperones are required for efficient Hsp104-mediated elimination of the yeast [PSI+] prion but not for prion propagation. Yeast 27:167–179. doi: 10.1002/yea.1742 PubMedGoogle Scholar
  27. Moriyama H, Edskes HK, Wickner RB (2000) [URE3] prion propagation in Saccharomyces cerevisiae: requirement for chaperone Hsp104 and curing by overexpressed chaperone Ydj1p. Mol Cell Biol 20:8916–8922CrossRefPubMedPubMedCentralGoogle Scholar
  28. Ness F, Cox BS, Wongwigkarn J, Naeimi WR, Tuite MF (2017) Over-expression of the molecular chaperone Hsp104 in Saccharomyces cerevisiae results in the malpartitioning of [PSI +] propagons. Mol Microbiol 104:125–143. doi: 10.1111/mmi.13617 CrossRefPubMedGoogle Scholar
  29. Park YN, Zhao X, Yim YI, Todor H, Ellerbrock R, Reidy M, Eisenberg E, Masison DC, Greene LE (2014) Hsp104 overexpression cures Saccharomyces cerevisiae [PSI +] by causing dissolution of the prion seeds. Eukaryot Cell 13:635–647. doi: 10.1128/EC.00300-13 CrossRefPubMedPubMedCentralGoogle Scholar
  30. Reidy M, Masison DC (2010) Sti1 regulation of Hsp70 and Hsp90 is critical for curing of Saccharomyces cerevisiae [PSI +] prions by Hsp104. Mol Cell Biol 14:3542–3552. doi: 10.1128/MCB.01292-09 CrossRefGoogle Scholar
  31. Reidy M, Masison DC (2011) Modulation and elimination of yeast prions by protein chaperones and co-chaperones. Prion 5:1–5. doi: 10.4161/pri.17749 CrossRefGoogle Scholar
  32. Reidy M, Sharma R, Shastry S, Roberts B-L, Albino-Flores I, Wickner S, Masison DC (2014) Hsp40s specify functions of Hsp104 and Hsp90 protein chaperone machines. PLoS Genet 10:e1004720. doi: 10.1371/journal.pgen.1004720 CrossRefPubMedPubMedCentralGoogle Scholar
  33. Saarikangas J, Barral Y (2016) Protein aggregation as a mechanism of adaptive cellular responses. Curr Genet 62:711–724. doi: 10.1007/s00294-016-0596-0 CrossRefPubMedGoogle Scholar
  34. Sarto-Jackson I, Tomaska L (2016) How to bake a brain: yeast as a model neuron. Curr Genet 62:347–370. doi: 10.1007/s00294-015-0554-2 CrossRefPubMedGoogle Scholar
  35. Schwimmer C, Masison DC (2002) Antagonistic interactions between yeast [PSI +] and [URE3] prions and curing of [URE3] by Hsp70 protein chaperone Ssa1p but not by Ssa2p. Mol Cell Biol 22:3590–3598CrossRefPubMedPubMedCentralGoogle Scholar
  36. Sharma D, Martineau CN, Dall MT Le, Reidy M, Masison DC, Kabani M (2009) Function of SSA subfamily of Hsp70 within and across species varies widely in complementing Saccharomyces cerevisiae cell growth and prion propagation. PLoS ONE 4:e6644. doi: 10.1371/journal.pone.0006644 CrossRefPubMedPubMedCentralGoogle Scholar
  37. Sporn ZA, Hines JK (2015) Hsp40 function in yeast prion propagation: amyloid diversity necessitates chaperone functional complexity. Prion 9:80–89. doi: 10.1080/19336896.2015.1020268 CrossRefPubMedPubMedCentralGoogle Scholar
  38. Stein KC, True HL (2014) Structural variants of yeast prions show conformer-specific requirements for chaperone activity. Mol Microbiol 93:1156–1171. doi: 10.1111/mmi.12725 PubMedPubMedCentralGoogle Scholar
  39. Tipton KA, Verges KJ, Weissman JS (2008) In vivo monitoring of the prion replication cycle reveals a critical role for Sis1 in delivering substrates to Hsp104. Mol Cell 32:584–591. doi: 10.1016/j.molcel.2008.11.003 CrossRefPubMedPubMedCentralGoogle Scholar
  40. Walsh P, Bursać D, Law YC, Cyr D, Lithgow T (2004) The J-protein family: modulating protein assembly, disassembly and translocation. EMBO Rep 5:567–571. doi: 10.1038/sj.embor.7400172 CrossRefPubMedPubMedCentralGoogle Scholar
  41. Wickner RB, Bezsonov E, Bateman DA (2014) Normal levels of the antiprion proteins Btn2 and Cur1 cure most newly formed [URE3] prion variants. Proc Natl Acad Sci USA 111:E2711–E2720. doi: 10.1073/pnas.1409582111 CrossRefPubMedPubMedCentralGoogle Scholar
  42. Winkler J, Tyedmers J, Bukau B, Mogk A (2012) Hsp70 targets Hsp100 chaperones to substrates for protein disaggregation and prion fragmentation. J Cell Biol 198:387–404. doi: 10.1083/jcb.201201074 CrossRefPubMedPubMedCentralGoogle Scholar
  43. Young JC (2010) Mechanisms of the Hsp70 chaperone system. Biochem Cell Biol 300:291–300. doi: 10.1139/o09-175 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Department of Genetics and BiotechnologySt. Petersburg State UniversitySt. PetersburgRussia
  2. 2.Laboratory of Amyloid BiologySt. Petersburg State UniversitySt. PetersburgRussia
  3. 3.St. Petersburg Branch, Vavilov Institute of General GeneticsRussian Academy of SciencesSt. PetersburgRussia
  4. 4.School of Biological SciencesGeorgia Institute of TechnologyAtlantaUSA
  5. 5.Institute of Translational BiomedicineSt. Petersburg State UniversitySt. PetersburgRussia

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